The Assembly Switch Mechanism of FtsZ Filament Revealed by All-Atom Molecular Dynamics Simulations and Coarse-Grained Models.

Dashuai Lv,Jingyuan Li,Sheng Ye

doi:10.3389/fmicb.2021.639883

Dashuai Lv, Jingyuan Li + Show 1 more

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https://doi.org/10.3389/fmicb.2021.639883

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Abstract

Bacterial cytoskeletal protein FtsZ binds and hydrolyzes GTP, and assembles into dynamic filaments that are essential for cell division. Here, we used a multi-scale computational strategy that combined all-atom molecular dynamics (MD) simulations and coarse-grained models to reveal the conformational dynamics of assembled FtsZ. We found that the top end of a filament is highly dynamic and can undergo T-to-R transitions in both GTP- and GDP-bound states. We observed several subcategories of nucleation related dimer species, which leading to a feasible nucleation pathway. In addition, we observed that FtsZ filament exhibits noticeable amounts of twisting, indicating a substantial helicity of the FtsZ filament. These results agree with the previously models and experimental data. Anisotropy network model (ANM) analysis revealed a polymerization enhanced assembly cooperativity, and indicated that the cooperative motions in FtsZ are encoded in the structure. Taken together, our study provides a molecular-level understanding of the diversity of the structural states of FtsZ and the relationships among polymerization, hydrolysis, and cooperative assembly, which should shed new light on the molecular basis of FtsZ’s cooperativity.

Highlights

FtsZ, an ancient tubulin-like GTPase, plays pivotal roles in dividing a cell into two daughter cells (Bi and Lutkenhaus, 1991)
Our study provides a molecular-level understanding of the diversity of the structural states of FtsZ and the relationships among polymerization, hydrolysis, and cooperative assembly, which should shed new light on the molecular basis of FtsZ’s cooperativity
We investigated the assembly dynamics of a Mycobacterium tuberculosis FtsZ (MtbFtsZ) trimer in different nucleotide-binding states using both all-atom Molecular dynamics (MD) simulations and coarse-grained models

Summary

Introduction

FtsZ, an ancient tubulin-like GTPase, plays pivotal roles in dividing a cell into two daughter cells (Bi and Lutkenhaus, 1991). FtsZ catalyzes the hydrolysis of GTP to GDP, which is coupled to its polymerization because the GTPase active site is completed at the interface between consecutive subunits (Mukherjee et al, 1993; Leung et al, 2004). Unlike tubulin that exhibits dynamic instability (Mitchison and Kirschner, 1984), FtsZ exhibits treadmilling (Bisson-Filho et al, 2017; Yang et al, 2017), which further directs the septal cell wall synthesis and cell division (BissonFilho et al, 2017; Yang et al, 2017). Treadmilling, characterized by polymerization at one end (i.e., plus end) and depolymerization at the other end (i.e., minus end), is coupled to GTPase activity and the GTPase-regulated conformational change of FtsZ subunits (Chen and Erickson, 2011; Li et al, 2013; Wagstaff et al, 2017).

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